Stem cell activity has been reported in various adult tissues and organs, including some discrete regions within the adult brain. The identification of a pool of cells within the mammalian CNS with the properties both to self-renew as well as differentiate into all neural cell types has generated much excitement in the neurobiology community because of its relevance to brain regeneration, injury and neoplasia. Our ability to harness the regenerative capacity of stem cells to reduce the burden of neurological disease and damage hinges on understanding the fundamental biology of these cells. Making progress in adult stem cell research is dependent on clearly identifying and isolating discrete cell populations, characterizing these cells, as well as on deciphering signals in the surrounding environment that instruct these cells whether to remain as stem cells or to differentiate. We previously isolated a cell surface receptor, CDOn, whose expression pattern strikingly coincides with regions in the adult central nervous system associated with stem cell activity. Interestingly, the loss of this gene function results in a microform of holoprosencephaly. The purpose of the experiments proposed here are to explore the possibility that CDOn receptor expression delineates the sup-population of slowly cycling stem cells in the adult brain. We plan to establish the identity of the cells in the stem cell niche that express CDOn and to substantiate the potential usefulness of CDOn expression as a marker for specifically isolating these cells in vitro and in vivo. Because CDOn is a receptor, we believe that revealing the identity of cells in the stem cell niche that express the CDOn receptor in comparison to cells that do not will yield insights into how cells respond differently to extrinsic cues within the microenvironment of the stem cell niche. [unreadable] [unreadable] [unreadable]